Search

Learning about the roles that duplicate genes play in the origins of novel phenotypes requires an understanding of how their functions evolve. To date, only one method—CDROM—has been developed with this goal in mind. In particular, CDROM employs gene expression distances as proxies for functional divergence, and then classifies the evolutionary mechanisms retaining duplicate genes from comparisons of these distances in a decision tree framework. However,CDROMdoes not account for stochastic shifts in gene expression or leverage advances in contemporary statistical learning for performing classification, nor is it capable of predicting the underlying parameters of duplicate gene evolution. Thus, here we developCLOUD, a multi-layer neural network built upon a model of gene expression evolution that can both classify duplicate gene retention mechanisms and predict their underlying evolutionary parameters. We show that not only is theCLOUDclassifier substantially more powerful and accurate thanCDROM, but that it also yields accurate parameter predictions, enabling a better understanding of the specific forces driving the evolution and long-term retention of duplicate genes. Further, application of theCLOUDclassifier and predictor to empirical data fromDrosophilarecapitulates many previous findings about gene duplication in this lineage, showing that new functions often emerge rapidly and asymmetrically in younger duplicate gene copies, and that functional divergence is driven by strong natural selection. Hence,CLOUDrepresents the best available method for classifying retention mechanisms and predicting evolutionary parameters of duplicate genes, thereby also highlighting the utility of incorporating sophisticated statistical learning techniques to address long-standing questions about evolution after gene duplication.

Background Gene duplication has played an important role in the evolution and domestication of flowering plants. Yet little is known about how plant duplicate genes evolve and are retained over long timescales, particularly those arising from small-scale duplication (SSD) rather than whole-genome duplication (WGD) events. Results We address this question in the Poaceae (grass) family by analyzing gene expression data from nine tissues of Brachypodium distachyon, Oryza sativa japonica (rice), and Sorghum bicolor (sorghum). Consistent with theoretical predictions, expression profiles of most grass genes are conserved after SSD, suggesting that functional conservation is the primary outcome of SSD in grasses. However, we also uncover support for widespread functional divergence, much of which occurs asymmetrically via the process of neofunctionalization. Moreover, neofunctionalization preferentially targets younger (child) duplicate gene copies, is associated with RNA-mediated duplication, and occurs quickly after duplication. Further analysis reveals that functional divergence of SSD-derived genes is positively correlated with both sequence divergence and tissue specificity in all three grass species, and particularly with anther expression in B. distachyon. Conclusions Our results suggest that SSD-derived grass genes often undergo rapid functional divergence that may be driven by natural selection on male-specific phenotypes. These observations are consistent with those in several animal species, suggesting that duplicate genes take similar evolutionary trajectories in plants and animals. Electronic supplementary material The online version of this article (10.1186/s12862-019-1415-2) contains supplementary material, which is available to authorized users.

Much of the enormous phenotypic variation observed across human populations is thought to have arisen from events experienced as our ancestors peopled different regions of the world. However, little is known about the genes involved in these population-specific adaptations. Here we explore this problem by simultaneously examining population-specific sequence and expression differentiation in four human populations. In particular, we design a branch-based statistic to estimate population-specific differentiation in four populations, and apply this statistic to single nucleotide polymorphism (SNP) and RNA-seq data from Italian, British, Finish, and Yoruban populations. As expected, genome-wide estimates of sequence and expression differentiation each independently recapitulate the known demographic history of these four human populations, highlighting the utility of our statistic for identifying genic targets of population-specific adaptations. Application of our statistic reveals that genes containing large copy number variations (CNVs) have elevated levels of population-specific sequence and expression differentiation, consistent with the hypothesis that gene turnover is a key reservoir of adaptive variation. Further, European genes displaying population-specific sequence and expression differentiation are enriched for functions related to epigenetic regulation, immunity, and reproduction. Together, our findings illustrate that population-specific sequence and expression differentiation in humans may preferentially target genes with CNVs and play important roles in a diversity of adaptive and disease-related phenotypes.

Gene duplication has played an important role in the evolution and domestication of flowering plants. Yet little is known about how plant duplicate genes evolve and are retained over long timescales, particularly those arising from small-scale duplication (SSD) rather than whole-genome duplication (WGD) events. Here we address this question in the Poaceae (grass) family by analyzing gene expression data from nine tissues ofBrachypodium distachyon,Oryza sativa japonica(rice), andSorghum bicolor(sorghum). Consistent with theoretical predictions, expression profiles of most grass genes are conserved after SSD, suggesting that functional conservation is the primary outcome of SSD in grasses. However, we also uncover support for widespread functional divergence, much of which occurs asymmetrically via the process of neofunctionalization. Moreover, neofunctionalization preferentially targets younger (child) duplicate gene copies, is associated with RNA-mediated duplication, and occurs quickly after duplication. Further analysis reveals that functional divergence of SSD-derived genes is positively correlated with both sequence divergence and tissue specificity in all three grass species, and particularly with anther expression inB. distachyon. Therefore, as found in many animal species, SSD-derived grass genes often undergo rapid functional divergence that may be driven by natural selection on male-specific phenotypes.

Gene duplication is a major source of new genes that is thought to play an important role in phenotypic innovation. Though several mechanisms have been hypothesized to drive the functional evolution and long-term retention of duplicate genes, there are currently no software tools for assessing their genome-wide contributions. Thus, the evolutionary mechanisms by which duplicate genes acquire novel functions remain unclear in a number of taxa. In a recent study, researchers developed a phylogenetic approach that uses gene expression data from two species to classify the mechanisms underlying the retention of duplicate genes (Proc Natl Acad Sci USA 110:1740917414, 2013). We have implemented their classification method, as well as a more generalized method, in the R package CDROM, enabling users to apply these methods to their data and gain insights into the origin of novel biological functions after gene duplication. The CDROM R package, source code, and user manual for the R package are available for download from CRAN at https://cran.rstudio.com/web/packages/CDROM/ . Additionally, the CDROM R source code, user manual for running CDROM from the source code, and sample dataset used in this manuscript can be accessed at www.personal.psu.edu/rua15/software.html . CDROM is the first software package that enables genome-wide classification of the mechanisms driving the long-term retention of duplicate genes. It is user-friendly and flexible, providing researchers with a tool for studying the functional evolution of duplicate genes in a variety of taxa.

Gene duplication provides raw material for the evolution of functional innovation. We recently developed a phylogenetic method to classify the evolutionary processes underlying the retention and functional evolution of duplicate genes by quantifying divergence of their gene expression profiles. Here, we apply our method to pairs of duplicate genes in eight mammalian genomes, using data from 11 distinct tissues to construct spatial gene expression profiles. We find that young mammalian duplicates are often functionally conserved, and that functional divergence gradually increases with evolutionary distance between species. Examination of expression patterns in genes with conserved and new functions supports the ?out-of-testes? hypothesis, in which new genes arise with testis-specific functions and acquire functions in other tissues over time. While new functions tend to be tissue-specific, there is no bias toward expression in any particular tissue. Thus, duplicate genes acquire a diversity of functions outside of the testes, possibly contributing to the origin of a multitude of complex phenotypes during mammalian evolution.

Levels of selective constraint vary among proteins. Although strong constraint on a protein is often attributed to its functional importance, evolutionary rate may also be limited if a protein is fragile, such that a large proportion of amino acid replacements reduce its fitness. To determine the relative contributions of essentiality and fragility to selective constraint, we compared relationships of selection against nonsense mutations (snon) and selection against missense mutations (smis) to protein sequence conservation (Ka). As expected, snon is greater than smis; however, the correlation between smis and Ka is nearly three times stronger than the correlation between snon and Ka. Moreover, examination of relationships to gene expression level, tissue specificity, and number of protein-protein interactions shows that smis is more strongly correlated than snon to all three measures of biological function. Thus, our analysis reveals that slowly evolving proteins are under strong selective constraint primarily because they are fragile, and that this association likely exists because allowing a protein to function improperly, rather than removing it from a biological network, can negatively affect the functions of other molecules it interacts with and their downstream products.

Piwi-interacting RNAs (piRNAs) are ≈30 nucleotide noncoding RNAs that may be involved in transposon silencing in mammalian germline cells. Most piRNA sequences are found in a small number of genomic regions referred to as clusters, which range from 1 to hundreds of kilobases. We studied the evolution of 140 rodent piRNA clusters, 103 of which do not overlap protein-coding genes. Phylogenetic analysis revealed that 14 clusters were acquired after rat–mouse divergence and another 44 after rodent–primate divergence. Most clusters originated in a process analogous to the duplication of protein-coding genes by ectopic recombination, via insertions of long sequences that were mediated by flanking chromosome-specific repetitive elements (REs). Source sequences for such insertions are often located on the same chromosomes and also harbor clusters. The rate of piRNA cluster expansion is higher than that of any known gene family and, in contrast to other large gene families, there was not a single cluster loss. These observations suggest that piRNA cluster expansion is driven by positive selection, perhaps caused by the need to silence the ever-expanding repertoire of mammalian transposons.

In this paper, we describe the results of a thorough survey in the four editions of the Brazilian Official Pharmacopoeia (FBRAS), in a search for data about the plants and other botanical products included in them. The growth of the pharmaceutical industry since the second half of last century markedly affected the Brazilian official medicine. The paper analyses the transformation within the Pharmacopoeia, focusing on the presence of Monographs for Native medicinal plants. The result showed a strong substitution of Native American medicinal plants by industrialized medicine and foreign medicinal plants in FBRAS and confirms the necessity of investiments in research for the validation of Brazilian Native plants. Este artigo descreve os resultados de uma extensa revisão efetuada nas quatro edições da Farmacopéia Brasileira, buscando dados sobre as plantas medicinais e outros produtos vegetais nela descritos. O crescimento da indústria farmacêutica internacional a partir da segunda metade do século passado afetou intensamente a medicina oficial no Brasil. O texto faz uma breve análise das transformações sofridas pela Farmacopéia, tomando como base a existência de Monografias para as espécies vegetais nativas. Os resultados do estudo demonstram uma intensa substituição das plantas nativas do Brasil por medicamentos industrializados e outros produtos vegetais estrangeiros, confirmando assim a necessidade de investimentos em pesquisa de validação das nossas plantas medicinais.

Este trabalho descreve os resultados obtidos em um levantamento realizado com 262 estudantes dos cursos de Farmacia e Biologia, de varias partes do Brasil, sobre o tema Plantas Medicinais e Fitoterapia. Foram aplicados questionarios com questoes relativas aos dados pessoais de cada estudante e questoes relacionadas a temas, como por exemplo: a) por que o estudante se interessava por Plantas Medicinais e Fitoterapia? e b) estudante deveria citar cinco plantas que mais conhecia e/ou utilizava. Os resultados da pesquisa demonstraram que os estudantes de Farmacia e Biologia reconhecem a importância das Plantas Medicinais e da Fitoterapia para o seu futuro desempenho como profissionais e tem interesse em se aprimorar nessa area de conhecimento. A alta frequencia de estudantes que consideraram a fitoterapia mais eficaz do que os medicamentos convencionais e a baixa frequencia daqueles que associaram plantas medicinais a riqueza da biodiversidade brasileira foram resultados preocupantes. Um ponto positivo foi o grande numero de citacoes de plantas medicinais que contam com algum estudo de validacao, como sendo as mais conhecidas e utilizadas. Consideramos interessante que as disciplinas dos Cursos de Farmacia e Biologia, envolvidas com o tema, concentrem‑se no estudo de plantas medicinais ja conhecidas e utilizadas pelos estudantes, capacitando‑os nos aspectos tecnico‑cientificos de cada especie e seus produtos.